AN AGE-RELATED GAMMA-DELTA T-CELL SUPPRESSOR ACTIVITY CORRELATES WITH THE OUTCOME OF AUTOIMMUNITY IN EXPERIMENTAL TRYPANOSOMA-CRUZI INFECTION
AN AGE-RELATED GAMMA-DELTA T-CELL SUPPRESSOR ACTIVITY CORRELATES WITH THE OUTCOME OF AUTOIMMUNITY IN EXPERIMENTAL TRYPANOSOMA-CRUZI INFECTION
复制标题
DOI：
10.1002/eji.1830231033
复制
发表时间：
1993-10-01
影响因子：
5.4
通讯作者：
MENGEL, J
中科院分区：
文献类型：
--
作者：
CARDILLO, F;FALCAO, RP;MENGEL, J
在这项工作中，从年轻和老年BALB/c小鼠感染克氏锥虫脾脏T细胞的抑制活性进行了比较，并与自身免疫性心肌炎的发展。从年轻的成年BALB/c小鼠急性克氏锥虫感染的T细胞表现出抑制活性时，加入到完全同种异体或MLS不同的混合淋巴细胞培养物。这种抑制不能被外源性白细胞介素（IL）-2逆转，也不直接依赖于IL-4，IL-10或转化生长因子β的存在。进一步表征的T细胞谱系负责的抑制活性，在体外和/或在体内消耗与α或γ δ T细胞受体的单克隆抗体显示，脾γ δ T细胞作为抑制淋巴细胞在幼年克氏锥虫感染的小鼠。此外，这些年轻的成年BALB/c小鼠不会发生自身免疫性心肌炎，并且在感染的早期慢性阶段表现出较低的同基因心脏移植排斥反应发生率。相反，急性感染的老年BALB/c小鼠的T细胞缺乏明显的T抑制活性。此外，这些小鼠早在感染开始后2个月就发生了严重的自身免疫性心肌炎，此时它们中的大多数排斥同基因心脏移植物。这些研究结果表明，γ δ T细胞介导的抑制机制可能在急性感染期间避免组织特异性耐受的破坏。此外，这种机制可能与免疫系统的时间生物学有关。
In this work the suppressive activity of splenic T cells from young and aged BALB/c mice infected with Trypanosoma cruzi were compared and correlated with the development of autoimmune myocarditis. The T cells from young adult BALB/c mice with acute T cruzi infection exhibit suppressor activity when added to full allogeneic or Mls-disparate mixed lymphocyte cultures. This suppression could not be reverted by exogenous interleukin (IL)-2 and was not directly dependent on the presence of IL-4, IL-10 or transforming growth factor-beta. Further characterization of the T cell lineage responsible for the suppressor activity by in vitro and/or in vivo depletion with monoclonal antibody to alphabeta or gammadelta T cell receptor revealed that splenic gammadelta T cells function as suppressor lymphocytes in young T cruzi-infected mice. In addition, these young adult BALB/c mice do not develop autoimmune myocarditis and showed a low incidence of syngeneic heart graft rejection in the early chronic phase of the infection. In contrast, T cells from acutely infected aged BALB/c mice lacked demonstrable T suppressor activity. Furthermore, these mice developed a severe autoimmune myocarditis as early as 2 months after the onset of the infection, when the majority of them reject syngeneic heart grafts. These findings suggest that a gammadelta T cell-mediated suppressor mechanism may operate in the avoidance of the breaking of tissue-specific tolerance during the acute infection. Moreover, such a mechanism is likely related to the immune system chronobiology.